Palatable elemental medical food

ABSTRACT

This invention relates to a palatable elemental nutritional formula that is nutritionally complete for humans with specialized dietary needs. The nutritional of the present invention uses specific free amino acids to provide the source of amino nitrogen (protein equivalents) and a special blend of fats that provides 38 to 50% of the total Calories in a pleasant tasting formula. The nutritionally complete formula of this invention is useful for children having multiple protein allergies, short gut syndrome, sick gut, diarrhea and the like. More specifically, the nutritional product, in accordance with this invention, utilizes L-asparagine monohydrochloride and L-glutamine in place of L-aspartic acid and L-glutamic acid, respectively. In addition, the source of fat comprises soy, fractionated coconut oil (medium chain triglycerides), high oleic safflower oil and esterified glycerol emulsifiers. The level of fat Calories is about 38 to 50% of total Calories, which produces a product having a low osmolarity and provides required energy requirements in a small volume.

This application is a continuation of U.S. application Ser. No.08/887,001 filed Jul. 2, 1997, now U.S. Pat. No. 5,922,766.

FIELD OF THE INVENTION

This invention relates to improved enteral nutritional hypoallergenicformulas and more particularly to hypoallergenic formulas which tastegood. In addition, the nutritional product of this invention provides anutritionally complete hypoallergenic food for individuals with multiplefood allergies, short gut syndrome, cystic fibrosis, pancreatic disease,gastroenteritis, inflammatory bowel disease, intractable diarrhea,malnutrition, protein maldigestion, infectious diseases or for patientswith hypermetabolism, such as burn and trauma victims or cancerpatients.

BACKGROUND OF THE INVENTION

Hypoallergenic formulas or compositions which are also referred to aselemental formulas, are characterized in that they containimmunologically unreactive protein hydrolysates or free amino acids. Theprotein hydrolysates comprises short peptide fragments and/or aminoacids instead of the intact protein found, for example, in cow's milkand soy protein based formulas. These short peptide fragments and freeamino acids have been found to be less immunogenic or allergenic thanintact proteins.

In addition to protein hydrolysates and/or free amino acids, mostnutritionally balanced elemental or hypoallergenic formulas containcarbohydrates, lipids, vitamins and minerals to provide a nutritionallycomplete formula. These formulas are utilized for feeding infants,children and adults who have allergies or sensitivities to intactprotein and are often medically used in the treatment of cysticfibrosis, chronic diarrhea, small bowel resection, steatorrhea andprotein-calorie malnutrition.

One well known problem in the preparation of elemental or hypoallergenicformulas is product instability. Extensive hydrolysis of the protein byacids, or enzymes is necessary to provide the short peptides and aminoacids utilized in the formulas to render such formulas hypoallergenic.These extensively digested proteins or free amino acids have undesirablecharacteristics such as bad taste and loss of capacity to emulsify fatand thereby fail to form physically stable emulsions that do notevidence phase separation.

U.S. Pat. No. 4,414,238 to Schmidl et al. discloses an elemental dietcomposition comprising carbohydrates, amino acids and/or low molecularweight peptides and lipids. The elemental diet of this patent has alipid component in the form of an emulsion consisting of lipids, anemulsifier selected from the group consisting of mono- anddi-glycerides, and a starch modified with succinic anhydride.

U.S. Pat. No. 4,670,268 to Mahmoud discloses an enteral nutritionalhypoallergenic formula which uses a starch modified by octenyl succinicanhydride, which is utilized as the sole lipid emulsifier, to provide anutritionally well-balanced dietary formula that possesses excellentphysical stability.

U.S. Pat. No. 5,411,751 to Crissinger discloses infant formulas whichcontain no more than subirritant levels of free, long-chain (C₁₆-C₂₂)fatty acids and triglycerides thereof. This patent teaches thatdigestion products of triglycerides, in particular, long-chain fattyacids and monoglycerides, can damage the intestinal epithelium ofinfants and thus could mediate the onset of disorders such asnecrotizing enterocolitis. This patent does not suggest or disclose apalatable elemental or hypoallergenic medical food that is essentiallyfree of L-glutamic acid and L-aspartic acid.

U.S. Pat. No. 5,234,702 to Katz et al. discloses a powdered nutritionalproduct that uses an antioxidant system to protect the oil componentcomprising ascorbyl palmitate, beta carotene and/or mixed tocopherolsand citrate. The teachings of this patent are incorporated herein byreference.

U.S. Pat. No. Re. 35,233, discloses a method of treating atrophy ofskeletal muscle and intestinal mucosa which comprises enterallyadministering glutamine or a functional derivative thereof in the rangeof 0.4 to 3.0 g/kg/day.

The nutritional formula according to this invention has been carefullyformulated to provide a nutritional product that can be the sole sourceof nutrition for patients consuming it. To provide effective nutritionto human infants, children and adults, the present invention, in itsmost specific embodiments, carefully considers the bioavailability oftrace and ultratrace minerals and the dietary interactions involvingtrace elements. Thus, the teachings of Forbes et al, Bioavailability ofTrace Mineral Elements, Ann. Rev. Nutr. 1983, 3:213-231 and Mills,Dietary Interactions Involving the Trace Elements, Ann. Rev. Nutr. 1985,5:173-193, are incorporated herein by reference.

U.S. Pat. Nos. 5,326,569 and 5,550,146 to Acosta et al. disclose ageneric powder base, rich in fats, carbohydrates, vitamins, minerals andtrace elements which are admixed with specific amino acids to yieldseveral different therapeutic products which are used in the nutritionalsupport of adults and children having various inherited metabolicdiseases. These patents do not suggest or disclose the nutritionallycomplete hypoallergenic formulas of this invention which are essentiallyfree of L-glutamic acid and L-aspartic acid.

The etiology of a number of gastrointestinal conditions has beendemonstrated to be caused in some cases by food protein allergens. Onesuch gastrointestinal condition is eosinophilic gastroenteritis.Eosinophilic gastroenteritis is characterized by peripheraleosinophilia, eosinophilic infiltration of the bowel wall, and variousgastrointestinal symptoms. In pediatric cases, food antigens are themost common cause of eosinophilic gastroenteritis. Administration of anelemental, hypoallergenic diet may be required for rapid recover as evenextensively hydrolyzed casein-based formulas such as Alimentum® ProteinHydrolysate Formula With Iron (Ross Products Division, AbbottLaboratories, Columbus, Ohio) contains peptide fragments large enough toevoke an allergic reaction in the most sensitive of allergicindividuals.

U.S. Pat. No. 5,492,899 to Masor et al. discloses an enteral nutritionalformula containing ribonucleotides at specified levels. The formula ofthis patent comprises carbohydrates, lipids, proteins, vitamins andminerals and four (4) specified nucleotides at specific levels andratios. One preferred embodiment of the present invention includes thepresence of nucleotides in the elemental hypoallergenic medical food.The teachings of U.S. Pat. No. 5,492,899 are incorporated herein byreference.

U.S. Pat. No. 5,340,603 to Neylan et al. relates to a hypercaloricformula which provides nutritional support for human infants havingchronic lung disease. The formula of this patent has a Caloric densityof at least 800 kcal per liter of formula and wherein not less than 56%of the total Calories in said formula is derived from fat. In addition,the hypercaloric formula of this reference contains not more than 15% oftotal Calories derived from a high quality protein source and from about20 to 27% of total Calories from a carbohydrate source. The formula ofthis patent also includes m-inositol at a concentration of at least 50mg per liter of formula.

U.S. Pat. No. 5,411,757 to Buist et al. relates to a balanced, palatablemedical diet for treatment of patients with inborn errors of essentialamino acid metabolism. The diet of this patent uses L-amino acids atspecified weights and ratios. More specifically, this patent discloses apalatable medical diet wherein the protein equivalent of L-amino acidsis formed by the acetylation or the esterification of the L-amino acids.In contrast, the present invention uses L-amino acids to supply theamino nitrogen (protein equivalent) except for the replacement ofL-asparagine for aspartic acid and L-glutamine for glutamic acid.

A presently available product known as Vivonex® Pediatric is marketed bythe Clinical Products Division of Sandoz Nutrition, Minneapolis, Minn.for the gastrointestinally impaired child. The Vivonex® Pediatriccontains 100% free amino acids and has an osmolality at standarddilution of 1 kcal/ml of 490 mOsm/kg H₂O. This product derives 25% oftotal Calories from fat with 68% of those Calories from medium chaintriglycerides.

Neocate® One+ marketed by Scientific Hospital Supplies, Inc. (SHS) NorthAmerica, Gaithersburg, Md., is a pediatric elemental nutritional that ismarketed in liquid and powdered forms and is designed for children overone year of age. This liquid product contains 100% of its amino nitrogenin the form of free L-amino acids and has an osmolality at standarddilution (100 kcal/100 ml) of 835 mOsm/kg H₂O. Neocate® One+ powder(unflavored), when mixed to yield 100 kcal/100 mL, has an osmolality of610 mOsm/kg H₂O. These products contain 3.5 grams of fat per 100 mL at aCaloric density of 100 kcal/100 mL. Neocate®, also marketed by SHS inthe U.K., Scandanavia and the USA, uses maltodextrin as the carbohydratesource, contains 11.4% of Calories from free L-amino acids and 44.3% ofCalories from fat wherein the fat is a mixture of refined lard, peanutoil and coconut oil.

In general, the prior art elemental or hypoallergenic formulas sufferfrom poor taste (organoleptic properties), high osmolarity and lowCaloric density. In contrast, the present invention has acceptableorganoleptic properties thereby facilitating oral consumption by thepatient which also increases patient compliance with diet restrictions.The improved organoleptic properties are accomplished in part, byessentially excluding L-glutamic acid and L-aspartic acid from theformula and replacing them with L-glutamine and L-asparaginemonohydrate. Further, the present invention is differentiated from theprior art in that it contains a higher Caloric content from fat whichassists in improving organoleptic properties; reduces osmolality andincreases overall Caloric density. Further, the specific fat blend ofthe invention provides a balance of the essential fatty acids linoleicand α-linolenic, in a readily absorbable form.

SUMMARY OF THE INVENTION

The present invention relates to an improved elemental formulacomprising carbohydrates, lipids, free L-amino acids, vitamins andminerals. The invention is based, in part, on the discovery that the useof medium chain triglycerides (MCT's) or fractionated coconut oil, soyoil, esterified glycerol emulsifiers and high oleic safflower oil as thelipid component, in combination with the use of L-asparagine monohydratein place of L-aspartic acid and L-glutamine in place of L-glutamic acid,vastly improved the organoleptic properties of the hypoallergenicformula. The present invention also uses a high level of fat to resultin a product having a low osmolarity and also provides needed energyrequirements in a mall volume.

One aspect of the present invention relates to the preparation of anelemental medical food that is essentially free of L-glutamic acid andL-aspartic acid. In the present invention, L-glutamic acid (C₅H₉NO₄,mol. wt. 147.13) is replaced with L-glutamine (C₅H₁₀N₂O₃, mol. wt.146.15), the monoamide of glutamic acid and L-aspartic acid (C₄H₇NO₄,mol. wt. 133.10) is replaced with L-asparagine monohydrate(C₄H₈N₂O₃•H₂O, mol. wt. 150.13), the monoamide of aspartic acid with onemolecule of water. As used herein and in the claims, the phrase “to beessentially free of L-glutamic acid and L-aspartic acid” means less than5 mgs of each acid should be present in 100 gms of powdered product(less than 50 ppm).

The present invention also relates to a complete pediatrichypoallergenic formula suitable for feeding to children on allergen-freediets. The formula according to this invention uses free L-amino acidsas the source of amino nitrogen and meets the recommended dietaryallowances (RDA) for the 1 to 3 year old child in 100 kcal and for the 4to 6 year old child in 1500 kcal. As used herein and in the claims, theterm “protein equivalent” means the amount of amino nitrogen in gramspresent in the formulation multiplied by 6.25.

There is disclosed an elemental medical food for administration to ahuman comprising a) a carbohydrate component which comprises from 38-56%of the total Caloric content of food; b) a lipid component whichcomprises from 38-50% of the total Caloric content of said food andwherein said lipid component is a blend of high-oleic safflower oil,fractionated coconut oil (medium chain triglycerides), soy oil andesterified glycerols; and c) an amino acid component which comprisesfrom 10-20% of the total Caloric content of said food and wherein theamino acid component is essentially free (less than 5 mgs per 100 gms ofpowdered product) of L-glutamic acid and L-aspartic acid. The term“essentially free” means each of the amino acids are at concentrationsof less than 5 mgs per 100 gms (50 ppm) of powdered product.

There is also disclosed a method for providing nutrition support to ahuman suffering from a malady selected from the group consisting ofmultiple food allergies, short gut syndrome, cycstic fibrosis,pancreatic disease, gastroenteritis, inflammatory bowel disease,intractable diarrhea, malnutrition, protein maldigestion, infectiousdiseases such as HIV, hypermetabolism, trauma, eosinophilicgastroenteritis and gastroesophogeal reflux; said method comprisesadministering to said human a hypoallergenic formula in accordance withthe present invention.

More specifically, this invention relates to an elemental medical foodand method of its use wherein the carbohydrate component comprises from38 to 56% of the total Caloric content of the composition and whereinthe lipid component comprises from 38 to 50% of the total Caloriccontent of the composition and wherein the amino acid or proteinequivalent component comprises from 10 to 20% of the total Caloriccontent of the composition. In a more preferred embodiment, the lipidcomponent comprises 38-46% of the total Caloric content of thecomposition. The lipid component of this invention supplies 2-8% by wt.of the powdered product as linoleic acid (5-15% of Calories) and 0.4 to1.0% by wt. of the powdered product as α-linolenic acid (0.8-2% of totalCalories).

Preferably, the carbohydrate component of this invention consistsessentially of corn syrup solids at a dextrose equivalent (DE) of 23 orless.

A stabilizer system is used in the formula of this invention and can bea single component or a mixture of known stabilizers. As mentionedpreviously, a major challenge in developing an elemental nutritional isphysical stability. Physical stability relates to the oil and wateremulsion of the formula. Those skilled in the art understand that freeamino acids and hydrolyzed proteins do not produce emulsions that arestable over time. It is important that the elemental medical foods ofthis invention possess acceptable physical stability as separation ofthe emulsion into water and oil phases greatly decreases thepalatability of the formula and may result in inadequate nutrition.

The inventors herein have evaluated numerous emulsion stabilizers andhave determined that esterified glycerol emulsifiers such as diacetyltartaric esters of monoglycerides are very useful in the presentinvention. Diacetyl tartaric acid esters of monoglycerides (hereinafter“DATEM”) are commercially available and generally regarded as safe forhuman consumption by the USFDA. Representative DATEM emulsionstabilizers useful in the present invention include the Panodan® line ofemulsion stabilizers sold by Grinsted Products, Inc. of Kansas, U.S.A.Panodan® is made from edible refined vegetable fat.

In one embodiment of the present invention, the DATEM emulsionstabilizer is the sole emulsion stabilizer and is present in theelemental medical food of this invention at a level of up to 8% byweight of the lipid. DATEM is grouped in the lipid component since upondigestion, esterases cleave the fatty acid moiety from the tartaric acidmoiety. The fatty acid then is absorbed and metabolized while thetartaric acid clears the body un-metabolized. The profile of Panodan®emulsion stabilizer sold by Grinsted is as follows:

Component Fatty Acid Wt % 14:0 0.1 16:0 6.6 18:0 54.5 18:1 0.3 20:0 0.4Diacetyl tartaric Acid 38.1

Another important aspect of the present invention relates to the use ofan antioxidant system to lessen oxidation of the lipid component. Thoseskilled in this art will appreciate that the use of unsaturated oils ina powdered elemental product present special problems. To overcome theoxidation (spoilage) of the oils in the powdered product, the presentinvention, in one preferred embodiment, uses an anti-oxidant systemcomprising ascorbyl palmitate, beta carotene and citrate. The teachingsof U.S. Pat. No. 5,234,702 to Katz et al., entitled ANTIOXIDANT SYSTEMFOR POWDERED NUTRITIONAL PRODUCTS, are incorporated herein by reference.

DETAILED DESCRIPTION OF THE INVENTION

All of the components of the inventive formulation are commerciallyavailable from numerous sources. For example, the carbohydrate sourcewhich is preferably corn syrup solids with a DE of less than 23 isavailable from Grain Processing Corporation, Muscatine, Iowa. The aminoacids are available from Kyowa Hakko, Ajinomoto and Tanabe of Japan, andDegussa of Germany. The lipids are available from Stephan Co., Maywood,N.J. and California Oils, Richmond, Calif. The L-glutamine component isavailable from Kyowa Hakko of Japan and the L-asparagine monohydrate isavailable from Degussa.

In accordance with this invention, the osmolality of the formula canrange from 300 to 400 mOsm/kg H₂O, and more preferably from 350 to 375mOsm/kg H₂O when 4.2 g of said powdered composition is added to water toyield 29.57 ml of formula. As one skilled in this art will appreciate,the osmolality of the formula will vary with the concentration orCaloric density of the formula. For example, at a Caloric density of 68kcal/100 ml, the osmolality of the RTF (ready-to-feed) formula can rangefrom 350-375 mOsm/kg H₂O. At a Caloric density of 135 kcal/100 ml, theosmolality of the formula can range from 850-900 mOsm/kg H₂O.

One aspect of the present invention resides in the use of corn syrupsolids for the carbohydrate source. It is important to use a source ofcarbohydrate that will not adversely affect (increase to a high value)the osmolality of the final product particularly when L-amino acidssupply the protein equivalent, since they are small molecules that addconsiderably to osmolality. Those skilled in the art will appreciatethat high osmolalities (i.e., above about 450 mOsm/kg H₂O for infantsand about 750 mOsm/kg H₂O for children) in a liquid nutrition productcan cause gastric upset and diarrhea. Thus, the use of types ofcarbohydrates, such as dextrose and sucrose, which would increase theosmolality above about 400 mOsm/kg H₂O for infants, and about 750mOsm/kg H₂O for children is discouraged. In a preferred embodiment, thecarbohydrate used in the present invention has a DE (dextroseequivalent) of no more than 23 and is corn syrup solids. Use of acarbohydrate with DE of greater than 23 in combination with L-aminoacids will provide an osmotic pressure in the intestine that may lead tobloating, diarrhea and dehydration. These are conditions that should beavoided in patients already suffering from gastrointestinal problems.The medical food in accordance with this invention provides a goodbalance of Caloric density and acceptable osmolality. As those skilledin this art will appreciate, as the DE of the carbohydrate increases,the osmolality of the formula will also increase. The preferred sourceof carbohydrates is corn syrup solids with a DE of 23 or less.

Also contemplated in this invention is an elemental medical food that isflavored. Flavorings and sweeteners (preferably not sucrose or glucose)known in the food industry are acceptable provided the consumingpatients are not allergic thereto and the osmolality of the finalproduct is acceptable. A vanilla flavored product sweetened with theartificial sweetener aspartame (NutraSweet®) was produced based onExample I. The osmolality of the flavored product at 68 kcal/100 ml was370 mOsm/kg H₂O and 895 mOsm/kg H₂O at 135 kcal/100 ml.

There is also disclosed a lipid component for use in the presentinvention which comprises on a weight percent of the lipid component, 35to 43% high oleic safflower oil, 28 to 35% fractionated coconut oil(MCT's), 24 to 30% soy oil, and 0.5 to 8% esterified glycerols. In thelipid component of this invention, the level of linoleic acid may rangefrom 15 to 22% and the level of α-linolenic may range from 2 to 5% byweight of the total lipid component.

A representative blend of 6.4 gms of soy oil, 9.0 gms of high oleicsafflower oil, 7.6 gms of fractionated coconut oil and 1.4 gms of DATEMwere incorporated into the elemental medical food according to thisinvention and then analyzed for fatty acid content. Table I sets forththe name of the fatty acid, gms of fatty acid per 100 gms powder, % ofenergy and weight % of fat.

TABLE I NO. OF G/100 G¹ % OF % OF FAT NAME CARBONS POWDER ENERGY WT.Caproic  C6:0 0.068 0.129 0.29 Caprylic  C8:0 4.230 8.015 18.00 CapricC10:0 3.032 5.745 12.90 Lauric C12:0 0.042 0.080 0.18 Palmitic C16:01.191 2.257 5.07 Palmitoleic C16:1n7 0.014 0.027 0.06 Stearic C18:01.159 2.196 4.93 Oleic C18:1n9 8.342 15.806 35.50 Linoleic C18:2n6 4.6538.816 19.80 α-Linolenic C18:3n3 0.531 1.006 2.26 Arachidic C20:0 0.0670.127 0.29 Eicosenoic C20:1n9 0.046 0.087 0.19 Behenic C22:0 0.051 0.0970.22 Lignoceric C24:0 0.024 0.045 0.10 Nervonic C24:1n9 0.018 0.034 0.08TOTALS 23.468 44.467 99.87 Monounsaturated 8.420 15.954 35.83 fattyacids Polyunsaturated 5.184 9.822 22.06 fatty acids Saturated fattyacids 9.864 18.690 41.97 ¹Analytical data

On analysis, one cannot differentiate the fatty acids from Panodan, soyoil and HO safflower oil.

In a further embodiment of the present invention, there is disclosed apowdered, elemental medical food which comprises per 100 g of powderfurther described in Table II.

TABLE II Elemental Medical Food Range Per 100 g Product Nitrogen, g2.32-2.92 Protein Equivalent, g 14.3-17.9 Fat, g 22.6-24.5 Moisture, g1.0-2.0 Ash, g 3.0-4.5 Carbohydrate, g 46.7-56.0 Calories 475-495 Vit.A, IU 1500-2256 Vit. E., IU 11.6-15.1 Vit. D, IU 260-317 Vit. K, mcg 70-103 Pyridoxine, mg 0.57-0.79 Niacin, mg  9.28-12.47 Folic acid, mcg177-282 Vit. B₁, mg 1.42-1.95 Riboflavin, mg 0.62-0.87 Vit. B₁₂, mcg4.06-6.46 Pantothenic acid, mg 5.05-8.03 Biotin, mcg 50-82 Vit. C, mg200-400 Total Choline, mg 36-65 Inositol, mg 32-42 Calcium, mg 515-600Phosphorous, mg 385-465 Ca/P 1.11-1.56 Magnesium, mg 40.0-60.0 Iron, mg 8.4-11.4 Zinc, mg 5.40-7.1  Manganese, mg 0.50-0.70 Copper, mg0.70-0.90 Iodine, mcg 28-56 Selenium, mcg 11.0-20.0 Chromium, mcg11.0-20.0 Molybdenum, mcg 12.0-26.0 Sodium, mg 217-257 Potassium, mg717-824 Chloride, mg 285-395 Taurine, mg 30-56 L-Carnitine, mg 23-31

Yet more specifically, the elemental food according to this inventioncomprises, based on 100 kcal of said composition, 2.8 to 3.8 g ofprotein equivalent, 4.0 to 5.6 g of fat, 9.0 to 11.8 g of carbohydrates,0.4 to 0.8 g linoleic acid, 262 to 473 IU Vitamin A, 40 to 80 IV VitaminD, 2.0 to 3.5 IU Vitamin E, 5 to 20 mcg Vitamin K, 0.11 to 0.42 mgthiamine, 0.1 to 0.21 mg riboflavin, 0.09 to 0.17 mg Vitamin B-6, 0.40to 1.36 mg Vitamin B-12, 1.6 to 3.2 mg niacin, 28 to 60 mcg folic acid,0.40 to 1.70 mg pantothenic acid, 4.0 to 18 mcg biotin, 8.6 to 85 mgVitamin C, 7.5 to 14.5 mg choline, 4.6 to 9.9 mg inositol, 4 to 6.5 mgL-carnitine, 103 to 127 mg calcium, 76 to 103 mg phosphorus, 8.0 to 12.7mg magnesium, 1.6 to 2.4 mg iron, 1.0 to 1.7 mg zinc, 0.10 to 0.15 mgmanganese, 0.11 to 0.19 mg copper, 6.7 to 11.8 mcg iodine, 2.2 to 4.7mcg selenium, 2.2 to 4.7 mcg chromium, 2.4 to 5.5 mcg molybdenum, 40 to55 mg sodium, 144 to 174 mg potassium and 55 to 85 mg chloride.

To convert values of nutrient per 100 kcal to values of nutrient per 100gms of powdered product, one multiplies the 100 kcal value by 4.75.

The inclusion of nucleotides and/or nucleotides in the elemental foodaccording to this invention is also contemplated. The teachings of U.S.Pat. Nos. 5,492,899 to Masor et al, 3,231,385 to Ziro et al., 4,544,599to Gil and 4,994,442 to Gil et al., which relate to the inclusion ofnucleotides in nutritional formulas, are incorporated herein byreference.

In another embodiment of the present invention, the protein equivalentcomponent of the elemental medical food has an amino acid profile as setforth in Table III.

TABLE III Amino Acid Profile of Protein Equivalent MINIMUM MAXIMUMgms/100 gms/100 MINI- MAXI- gms* gms* MUM** MUM** L-alanine 2.86 4.232.80 4.41 L-arginine 5.17 7.72 5.05 7.93 L-asparagine 8.37 12.42 8.3513.10 L-cystine 1.10 1.68 1.10 1.72 L-glutamine 10.62 15.85 10.44 16.41Glycine 2.20 3.29 2.20 3.45 L-histidine 2.20 3.29 2.14 3.38 L-isoleucine5.72 8.53 5.60 8.83 L-leucine 9.25 13.83 9.12 14.28 L-lysine 5.17 7.665.05 7.93 L-methionine 2.15 3.22 2.09 3.31 L-phenylalanine 4.79 7.124.67 7.31 L-proline 2.92 4.16 2.80 4.41 L-serine 2.86 4.23 2.80 4.41L-threonine 3.80 5.71 3.74 5.86 L-tryptophan 1.49 2.22 1.42 2.28L-tyrosine 4.79 7.12 4.67 7.31 L-valine 6.55 9.74 6.43 10.07 *of aminoacids **as percent of protein equivalent

The Caloric density of the inventive formula is preferably from about450 to 500 kcal/100 g of powder. The Caloric density of the RTF productcan, of course, be adjusted through rate of dilution with water.

This invention relates to improved enteral nutritional hypoallergenicformulas and more particularly to hypoallergenic formulas which tastegood. In addition, the nutrition product of this invention provides anutritionally complete hypoallergenic food for individuals with multiplefood allergies, short gut syndrome, cystic fibrosis, pancreatic disease,gastroenteritis, inflammatory bowel disease, intractable diarrhea,malnutrition, protein maldigestion, infectious diseases or for patientswith hypermetabolism, such as burn and trauma victims or cancerpatients.

The present invention also relates to a method for providing nutritionalsupport to a human suffering from gastrointestinal conditions caused byfood protein allergens or severe food allergies. The method comprisesthe enteral administration of the hypoallergenic medical food accordingto this invention to a human suffering from a protein allergen inducedgastrointestinal condition.

The elemental food according to this invention is for enteraladministration and is designed to provide complete nutrition (meets allRDA's) in a small volume. For example, when the RDA for energy for ageis supplied by the instant elemental food, all nutrients meet both theUSFDA Infant Formula Act specifications and RDA for age in volumes notedin Table IV.

TABLE IV Elemental Add H2O to Age Food, g Make (mL) Fl Oz kcal/oz 0 < 6mo 137   800 27 24 6 < 12 mo 179   930 31 27 1 < 4 yr. 274 1,272 43 30 4< 7 yr. 379 1,330 45 40 7 < 11 yr. 421 1,478 50 40

The following Table V is a representative listing of ingredients and arange of % by weight for each component that can be used to prepare thepalatable elemental medical food of this invention.

TABLE V Bill of Materials Ingredient Per 100 lbs. powder* PediatricElemental Base Maltrin M200 53 lbs Tricalcium phosphate 1.30 lbDipotassium phosphate 1.1927 lb Sodium citrate 0.7451 lb Potassiumcitrate 0.9258 lb Magnesium chloride 0.34 lb Calcium carbonate 0.1702 lbSodium chloride 0.036 lb Potassium Iodide 0.000055 lb High OleicSafflower Oil 8.9 lb MCT oil 7.5 lb Soy oil 6.4 lb Panodan 1.42 lbVitamin A, D3, E, K1 Concentrate 0.0338 lb Refined coconut oil 7.86 gVitamin E acetate 6.90 g Vitamin A acetate 540 mg Phylloquinone(phytonadione) 26.1 mg Vitamin D3 3.83 mg Ascorbyl Palmitate 0.0282 lbBeta Carotene 0.0009 lb Ascorbic Acid 0.4343 lb L-carnitine 0.0269 lbVitamin/Mineral/Taurine premix 0.2002 lb Calcium phosphate, dibasic(premix diluent) 25.4 g Taurine 25.0 g m-Inositol 18.4 g Zinc sulfate7.59 g Niacinamide 5.25 g Ferrous sulfate 2.90 g d-Calcium pantothenate2.84 g Cupric sulfate 1.57 g Thiamine chloride hydrochloride 804 mgRiboflavin 355 mg Pyridoxine hydrochloride 326 mg Manganese sulfate 187mg Folic acid 99.9 mg Biotin 28.7 mg Sodium selenite 14.1 mgCyanocobalamin 2.29 mg Choline chloride 0.0584 lb Ferrous sulfate 0.0324lb Potassium citrate 0.0020 lb Manganese sulfate 0.0011 lb Chromiumchloride 0.00005 lb Sodium molybdate 0.00004 lb Amino Acid Premix: 17.24lb L-Glutamine 875.4 g L-Asparagine monohydrate 780.2 g L-Leucine 762.0g L-Lysine acetate 598.7 g L-Valine 539.8 g L-Isoleucine 471.7 gL-Arginine 426.4 g L-Phenylalanine 394.6 g L-Tyrosine 394.6 gL-Threonine 313.0 g L-Proline 240.4 g L-Alanine 235.9 g L-Serine 235.9 gGlycine 181.4 g L-Histidine 181.4 g L-Methionine 176.9 g L-Cystinedihydrochloride 122.5 g L-Tryptophan 122.5 g TOTAL 99.99 lb* *values inkilograms are set forth in Table VII

A specific embodiment of an elemental formula in accordance with thepresent invention is set forth in Table VI.

TABLE VI NUTRIENT PER 100 G POWDER Protein Equivalent, g 14.3 Fat, g22.6 Carbohydrate, g 46.7 Linoleic acid, g 2.85 Linolenic acid, g 0.48Calories, kcal 475 Calcium, mg 515 Phosphorus, mg 385 Magnesium, mg 40Sodium, mEq (mg) 9.35 (215) Potassium, mEq (mg) 18.29 (715) Chloride,mEq (mg) 8.04 (285) Iron, mg 8.4 Zinc, mg 5.3 Copper, mg 0.60 Iodine,mcg 34 Manganese, mg 0.50 Selenium, mcg 11 Vitamin A, mcg RE (IU) 390(1300)   Vitamin D, mcg (IU) 5 (200) Vitamin E, mg α-TE (IU) 6.7 (10.0) Vitamin K, mcg 30 Vitamin C, mg 43 Thiamin, mg 1.0 Riboflavin, mg 0.5Vitamin B-6, mg 0.48 Vitamin B₁₂, mcg 2.0 Niacin, mg 8.0 Folic Acid, mcg140 Pantothenic Acid, mg 2.0 Biotin, mcg 20 Choline, mg 38 Inositol, mg24 Chromium, mcg 11 Molybdenum, mcg 12 Taurine, mg 30 L-carnitine, mg 23

The present invention will now be explained on the basis of somespecific embodying examples, which, however, are to be considered asillustrative only. Unless otherwise noted, concentrations are parts byweight.

EXAMPLE 1 General Procedures

The teachings of U.S. Pat. No. 5,326,569 to Acosta et al. regarding thepreparation of the amino acid mixtures and the process of preparing anelemental formula, are used in the preparation of the elemental formulasaccording to this invention and are thus incorporated herein byreference. An enteral formula in accordance with this invention is ingeneral, accomplished through the dry blending of a powdered premix basewith an amino acid premix. The production of the premixed base isaccomplished through the steps summarized below:

1. Preparation of Stock Solutions:

a. Preparation of a water soluble vitamin and trace mineral mixture;

b. Preparation of an ascorbic acid mixture;

c. Preparation of oil blend containing oil soluble vitamins; and

d. Preparation of a carbohydrate/mineral slurry;

2. Combination in a specified sequence of the Stock Solutions:

a. Mixing of the oil blend and carbohydrate/mineral slurry;

b. Addition of the water soluble vitamins to the slurry; and

c. Addition of ascorbic acid to the slurry.

3. Drying of the combined stock solutions to yield the powdered premixbase.

4. Dry blending of the powdered premix base, with an amino acid premixto yield the elemental formula according to the present invention.

Commercial Scale

The clinical product utilized in Example 2 was produced on a commercialscale. A batch of 1,000 kg was produced using the method described aboveto insure label composition over shelf life as set forth in Table VII.

TABLE VII INGREDIENTS AMOUNT (kg) MCT Oil 75.000 Soy Oil 64.000 HOSafflower Oil 89.000 Oil Soluble Vit. Premix 0.338 Panodan 14.200 SodiumCitrate 7.451 Sodium Chloride 0.360 Potassium Citrate 9.258 PotassiumIodide 0.0005 Magnesium Chloride 0.340 Potassium Phosphate Dibasic 7.451Calcium Carbonate 1.702 umTCP (Ultramicronized Tricalcium Phosphate)1.300 Maltrin M200 530. Ferrous Sulfate 0.324 Premix 1870 2.002Manganese Sulfate 0.011 Choline Chloride 0.584 L-Carnitine 0.269Chromium Chloride 0.005 Sodium Molybdate 0.003 Ascorbic Acid 4.343 BetaCarotene 0.009 Ascorbyl Palmitate 0.282 L-Alanine 5.70 L-AsparagineMonohydrate 19.15 Glycine 4.45 L-Arginine 10.40 L-Cystine 2-HCl 3.00L-Glutamine 21.45 L-Histidine 4.45 L-Isoleucine 11.55 L-Lysine Acetate14.65 L-Leucine 18.70 Phenylalanine 9.65 L-Threonine 7.70 L-Tryptophan3.00 L-Tyrosine 9.65 L-Valine 13.20 L-Methionine 4.30 Proline 5.70Serine 5.70 TOTAL 1000.06

EXAMPLE 2

A clinical study of the inventive formula was conducted at The JohnsHopkins Hospital (Baltimore, Md.) to assess the growth, tolerance andbiochemical response of children fed the formula according to thepresent invention as a primary feeding for four (4) months. Thechildren, while consuming the inventive formula, were on diets free fromknown food allergens to which they were sensitive. The primaryindicators used to evaluate the formula according to the invention wereweight, height, intake, stool patterns, blood biochemistry (completeblood count, serum albumin, ferritin, transthyretin, retinol bindingprotein, retinol and urea nitrogen, and plasma amino acids), and stooloccult blood assessment. Secondary variables included gastrointestinalsymptoms.

The non-randomized feeding study was conducted with fourteen (14)children with protein sensitive eosinophilic gastroenteritis or multiplefood protein sensitivity. Each child serves as his/her own control. Allsubjects prior to admission to the study were subjected to a doubleblind, placebo-controlled food challenges with the child's currentformula and the inventive composition to determine if it elicited anyallergic symptoms. Previous medical records, growth history for up tothe past twelve (12) months, detailed medical and dietary histories andrecords of oral challenge results for each subject were obtained.

The elemental product produced in Example 1 was provided as a powder in350 g cans and was reconstituted to meet the individualized needs ofeach child as determined by the research dietitian. The inventiveformula was flavored with approved flavorings determined by theinvestigator. Children were allowed to ingest only those foods thatcould be tolerated, the study formula and flavorings approved by theinvestigator.

On Day 1 of the study, blood and stool samples were collected andsubjects were again assessed at one (1) and four (4) month post-startdates for growth, formula intake, tolerance and blood and stoolparameters (4 months only).

Subjects were removed from the study on the basis of a protocol failureor a treatment failure. A child was considered a protocol failure if heor she failed to comply with schedule examinations, was voluntarilyremoved by the parent, failed to consume sufficient amounts of the studyformula or removed by the physician because he or she believed it was inthe child's best interest. Children were considered a treatment failureif they were unable to consume the study formula due to intolerance oran allergic reaction to the study formula.

Careful measurements of weight, height and head circumference were madeupon enrollment into the study, at each visit and at study exit usingstandard techniques and equipment. Available weight and height datacollected during the one-year period prior to the start of the studywere used for historical comparisons.

At the four-month point, the elemental product produced in Example I wassupplying an average of 58% of total calories per day for the children,with the remainder being supplied by authorized (i.e., tolerized foods)foods. In general, the children maintained growth while on the studyformula. Only one subject experienced a slight decrease in rate ofgrowth while consuming the study formula and this may have been causedby problems at home (parental separation).

The children in the study often had little appetite for solid foods andweight gains would have improved if energy intakes were increased tomeet the recommended RDA. Hemoglobin and hematocrit concentrations instudy subjects were significantly improved during the study period.Other blood chemistries assessed were generally maintained at levelssimilar to those at entrance. Insufficient data were available at thetime of filing this application to assess the effect of the studyformula on serum vitamins. Data is continuing to be collected in thisstudy and will be statistically analyzed.

Stool patterns improved slightly during the study period; in fact, twochildren were able to be toilet trained after going on the study formuladue to improvement in their stools compared to their previous feeding.

In conclusion, the preliminary results of the study support for formulaaccording to the invention is a hypoallergenic formula suitable for usein the management of children with multiple food allergies or allergiceosinophilic gastroenteritis. Children grew acceptably on the inventiveproduct when it provided the majority of the energy needs. The childrentolerated the study product well and found its taste acceptable.Anecdotal comments from parents and site personnel have been positive.Data continue to be collected and statistical analysis will be conductedat the conclusion of data collection.

EXAMPLE 3

The hypoallergenic formula in accordance with this invention wasanalyzed for protein efficiency ratio (PER), which is a measure ofprotein quality using laboratory rats. PER is determined by dividing theanimals weight gain by protein intake. Two groups of ten rats each, werefed a diet for 28 days of the hypoallergenic formula and a casein basedformula using AOAC method-960.48, AOAC Official Methods of Analysis,15th Edition, 1990. Every seven days, the rats were weighed and theirfood consumption was recorded. At the end of 28 days, the total weightgain and protein composition of the two groups were calculated. Thesevalues were used to calculate the PER.

The results of this rat bioassay, set forth in Table VIII, indicate thatthe pediatric elemental diet, in accordance with the present inventionhas a significantly greater protein efficiency ratio than theconventional casein based formula.

TABLE VIII Body Weights - Grams Animal Week Week Week Week Week Wt. No.0 1 2 3 4 Gain CASEIN COMPOSITION 1 76 86 124 158 199 123 2 71 88 130170 199 128 3 72 90 122 150 190 118 4 72 86 133 159 201 129 5 82 94 123153 191 109 6 79 107 150 192 232 153 7 75 91 125 159 212 137 8 78 89 127158 195 117 9 68 85 119 149 197 129 10  74 96 129 163 197 123 Mean 75 91128 161 201 127 SD 4.19 6.52 8.73 12.57 12.27 12.05 PEDIATRIC ELEMENTAL1 71 96 133 184 237 166 2 70 93 133 179 245 175 3 81 99 137 187 237 1564 75 97 145 267 266 191 5 76 97 133 174 212 136 6 67 95 133 187 236 1697 84 111 167 232 293 209 8 80 103 144 200 247 167 9 73 100 146 190 233160 10  74 96 145 183 231 157 Mean 75 99 141 192 244 169 SD 53 5.0810.72 17.19 22.11 20.14 Feed Consumption - Grams Animal Wk Wk Wk Wk No.1 2 3 4 Total Protein PER CASEIN COMPOSITION 1 62 102 116 133 412 422.92 2 78 120 149 133 479 48.9 2.62 3 71 94 110 123 399 40.7 2.89 4 62113 114 139 428 43.7 2.6 5 73 95 104 128 399 40.7 2.67 6 90 118 133 138479 48.8 3.12 7 75 104 121 138 438 44.7 3.06 8 62 110 115 133 421 42.92.73 9 67 90 109 130 396 40.4 3.2 10  85 98 124 125 432 44.1 2.79 Mean73 104 119 132 428 43.7 2.9 SD 9.74 10.39 13.23 5.52 30.4 3.1 0.195PEDIATRIC ELEMENTAL 1 81 101 134 144 460 45 3.69 2 80 105 129 157 47246.3 3.78 3 79 109 139 166 492 48.2 3.23 4 79 115 150 158 502 49.2 3.895 77 97 122 144 439 43.1 3.16 6 80 106 137 143 466 45.6 3.70 7 90 136163 162 551 54 3.87 8 86 116 146 147 489 48 3.48 9 90 121 131 129 47146.1 3.46 10  80 113 124 134 450 44.1 3.56 Mean 82 111 137 148 479 46.93.58 SD 4.67 11.1 12.6 12.23 31.74 3.11 0.253

EXAMPLE 4 Immunogenicity

This experiment was conducted to evaluate the allergenic potential ofthe elemental medical food of this invention (produced in Example 1)compared to three commercially available hypoallergenic nutritionals.Low immunogenicity demonstrated in this experiment is highly predictiveof very low allergenic activity of a nutritional product.

The three commercially available products were Neocate®, Neocate® One+and Vivonex® Pediatric. In this experiment, rabbits were hyperimmunizedwith the nutritional according to this invention or the aforementionedcommercial products using a vigorous immunization protocol employingComplete Freunds' Adjuvant (CFA) with multiple injections. Enzyme-linkedimmunoabsorbent assay (ELISA) was used to measure the systemic (IgG)antigen-specific immune response of the rabbits and to define therelative immunogenicity of each product. A more detailed understandingof immunogenicity evaluation of proteins can be obtained from a reviewof the following articles:

1) Cordle et al., “Immunogenicity Evaluation of Protein Hydrolysates forHypoallergenic Infant Formula”, J. of Ped. Gastro. and Nut., 13:270-276(1991);

2) Cordle, “Control of Food Allergies Using Protein Hydrolysates”, FoodTechnology, October 1994; and

3) Cordle et al., “Evaluation of the immunogenicity of proteinhydrolysate formulas using laboratory animal hyperimmunization”,Pediatr. Allergy Immunol, 5:14-19, (1994).

The teachings of the three listed articles are incorporated herein byreference.

Samples of each product were mixed with sterile phosphate bufferedsaline (PBS) to result in a concentration of 5 mg protein (amino acids)per 1.5 ml (PBS solution). The primary immunization was prepared byemulsifying 1.5 ml of the PBS product solution with 3.0 ml of CFA. Thebooster immunization was prepared by mixing 1.5 ml of each PBS solutionwith 1.5 CFA. These samples were then administered at a dose of 5 mgprotein equivalent per each of two immunizations.

The animals were placed on a vegetable diet (milk, soy and rice free)for 14 days prior to the primary immunization and remained on this dietfor the duration of the study. Pre-immunization blood samples were takenfrom each rabbit on day 0, and then each rabbit was immunized. On day21, a second immunization was conducted. The animals were exsanguinatedon day 35. Serum was collected and stored at −20° C. until testing.

Antibody responses were quantitated by an ELISA developed for eachantigen as follows. ELISA plates were coated with the immunizing formulaat an optimal (saturating) concentration. The plates were blocked withPBS containing 0.05% egg albumin and 0.1% Tween 20 to eliminatenon-specific binding. Test antisera were serially diluted and added tothe coated plates. Next goat anti-rabbit IgG horseradish peroxidaseconjugate was added to react with any rabbit antibody bound to theimmunogen. Addition of the enzyme substrate (tetramethylbenzidine)caused a color change that was directly proportional to the amount ofantibody bound. Antibody titer was defined as the reciprocal of thedilution of serum which gave an ELISA optical density of 0.3 at 450 nm10 minutes after the enzyme substrate addition.

Five (5) rabbits were immunized with each nutritional product. The datacontained in Table IX sets forth the mean titer for each group of fiverabbits and the standard deviations on day 0 and day 35.

TABLE IX FORMULA DAY MEAN TITER SD Ex. 1  0    21    12 35   119*    83Neocate  0    92    24 35   389*   222 Neocate One +  0   351   111 3556,000 27,505 Vivonex Pediatric  0   304   185 35   646*   469 SD =standard deviation *= not significantly different

While the titers for the formula according to this invention wereactually lower than all of the commercial products, it can only beconcluded that the elemental formula produced in Ex. I was far superiorto Neocate One+. It can also be concluded that the formula according tothe invention demonstrates very low immunogenicity, indicating that theproduct according to the invention will demonstrate clinicalhypoallergenic performance. Further, these data support the use of theinstant invention for people that are exquisitely sensitive to milkproteins or that react to extensively hydrolyzed protein formulas.

EXAMPLE 5 Organoleptic Test

One important aspect of this invention resides in the taste of theformula made in accordance with the invention. Most elemental medicalfoods presently available have a highly unpleasant taste and, as such,patients using these formulas are less likely to consume the necessaryCaloric intake or may even be non-compliant with therapy.

The elemental medical food produced in Example 1 was taste testedagainst four commercially available formulas. The product name andsample number for each product evaluated is set forth in Table X.

TABLE X SAMPLE COMMERCIAL NAME SUPPLIER Ex. 1 Present Invention AbbottLaboratories A Vivonex Pediatric Sandoz Nutrition Company B Neocate SHSC Neocate One + SHS D Elemental 028 SHS

All samples were supplied as unflavored powders and were reconstitutedwith water as shown in Table XI.

TABLE XI SAMPLE WT. OF POWDER WT. OF WATER Ex. 1 354 g 1301 g  A 194 g594 g B 342 g 1420 g  C 100 g 340 g D 200 g 674 g

Fifty-one (51) volunteers were recruited to evaluate the relativeacceptability of a formula according to this invention compared to the 4commercially available elemental medical foods. The procedure for thisorganoleptic evaluation consisted of providing a sample of the inventiveformula to each evaluator, having them taste it and the comparing thetaste of the 4 commercial formulas to the taste of the inventiveformula. Each sample was evaluated at 24° C. and evaluated with thefollowing scale:

9=Extremely better than Ex. 1

8=Very much better than Ex. 1

7=Moderately better than Ex. 1

6=Slightly better than Ex. 1

5=Neither better nor worse than Ex. 1

4=Slightly worse than Ex. 1

3=Moderately worse than Ex. 1

2=Very much worse than Ex. 1

1=Extremely worse than Ex. 1

The raw data from each evaluator was collected. Means, standarddeviations and p-values were calculated. Significance was determined atthe 95% Confidence Level, Turkey Criteria. Comparison of Ex. 1 wasconsidered significant if the p-value was <0.0125, using BonferroniCriteria. The results of this organoleptic test are set forth in TableXII.

TABLE XII STATISTICAL SAMPLE MEAN GROUP P < or > 5 A 2.63 C 0.0000 B4.16 B 0.0000 C 5.08 A 6.6623 D 5.06 A 0.7433

Samples which share a letter under the heading Statistical Group are notsignificantly different. From the data presented in Table IX, it isevident that commercial products A and B were significantly worse thanEx. I. Thus, the formula according to this invention provides anelemental medical food that possesses highly acceptable flavor.

Industrial Applicability

This invention provides a palatable, hypoallergenic/elemental productfor the nutritional maintenance of humans that suffer from proteinallergies. The medical community is constantly in search of improvedformulations for their patients that supply a complete diet in apleasant tasting matrix. As demonstrated in the examples, the formula inaccordance with the present invention is easily measured and providesacceptable growth and tolerance to patients consuming same.

The embodiments of the present invention may, of course, be carried outin other specific ways than those set forth herein without departingfrom the spirit and essential characteristics of the invention. Thepresent embodiments are therefore, to be considered in all respects asillustrated and not restrictive.

We claim:
 1. A method for providing nutrition support to a humansuffering from food protein allergens, said method comprises the enteraladministration of a hypoallergenic medical food suitable for use as thesole source of nutrition comprising: a) a carbohydrate component whichcomprises from 38 to 56% of the total Caloric content of said food; b) alipid component which comprises from 38 to 50% of the total Caloriccontent of said food and in which said lipid component comprises, basedupon the weight of the lipid component, 35 to 43% high-oleic saffloweroil, 28 to 35% fractionated coconut oil, 0.5 to 8% esterified glycerolsand 24 to 30% soy oil; and c) a free amino acid component whichcomprises from 10 to 20% of the total Caloric content of said food andwherein said amino acid component comprises, based upon the weight ofthe hypoallergenic food, less than 50 ppm of L-glutamic acid and lessthan 50 ppm of L-aspartic acid.
 2. The method according to claim 1wherein the hypoallergenic medical food comprises, based on 100 kcal ofsaid composition: 2.8 to 3.8 g protein equivalent; 4.0 to 5.6 g fat, 9.0to 11.8 g carbohydrate; 0.4 to 0.8 linoleic acid; 262 to 475 IU VitaminA; 40 to 80 IU Vitamin D; 2.0 to 3.5 IU Vitamin E; 5 to 20 mcg VitaminK; 0.11 to 0.42 mg thiamine, 0.1 to 0.21 mg riboflavin; 0.09 to 0.17 mgVitamin B-6; 0.40 to 1.36 mcg Vitamin B-12; 1.6 to 3.2 mg niacin; 28 to60 mcg folic acid; 0.40 to 1.70 mg pantothenic acid; 4.0 to 18.0 mcgbiotin; 8.6 to 85 mg Vitamin C; 7.5 to 14.6 mg choline; 4.6 to 9.9 mginositol; 4.0 to 6.5 mg L-carnitine; 103 to 127 mg calcium; 76 to 103 mgphosphorus; 8.0 to 12.7 mg magnesium; 1.6 to 2.4 mg iron; 1.0 to 1.7 mgzinc; 0.10 to 0.15 mg manganese; 0.11 to 0.19 mg copper, 6.7 to 11.8 mcgiodine; 2.2 to 4.7 mcg selenium; 2.2 to 4.7 mcg chromium; 2.4 to 5.5 mcgmolybdenum; 40 to 55 mg sodium; 144 to 174 mg potassium and 55 to 85 mgchloride.
 3. The method according to claim 1 wherein said free aminoacid component comprises, based upon the weight of the free amino acidcomponent: 2.3 to 3.2 wt %—L-histidine; 5.9 to 8.5 wt %—L-isoleucine;9.5 to 14.0 wt %—L-leucine; 6.6 to 9.7 wt %—L-valine; 5.2 to 7.6 wt%—L-lysine; 2.2 to 3.2 wt %—L-methionine; 4.9 to 7.1 wt%—L-phenylalanine; 3.8 to 5.7 wt %—L-threonine; 1.4 to 2.2 wt%—L-tryptophan; 3.0 to 4.2 wt %—L-alanine; 5.3 to 7.7 wt %—L-arginine;8.6 to 12.4% L-asparagine monohydrate; 1.1 to 1.9% L-cystinedihydrochloride; 11.0 to 15.8 wt %—L-glutamine; 2.3 to 3.2 wt %—glycine;3.0 to 4.1 wt % L-proline; 3.0 to 4.2 wt %—L-serine; and 5.0 to 7.1 wt%—L-tyrosine.
 4. The method according to claim 1 wherein saidcarbohydrate component consists essentially of corn syrup solids with aDE of 23 or less.
 5. The method according to claim 1 wherein saidhypoallergenic medical food is in powder form.
 6. The method accordingto claim 1 wherein said hypoallergenic medical food additionallycomprises at least one element selected from the group consisting ofnucleotides, nucleotides, antioxidant system, natural flavor, artificialflavors, artificial sweeteners, major trace and ultratrace minerals,minerals, vitamins and m-inositol.
 7. The method according to claim 1wherein said carbohydrate component is corn syrup solids with a DE of 23or less; said lipid component comprises 35 to 41% by wt high oleicsafflower oil, 28 to 35% by wt fractionated coconut oil, 24 to 30% by wtsoy oil and 0.5 to 8% by wt of diacetyl tartaric acid esters ofmonoglycerides; and said free amino acid component comprisesL-asparagine monohydrate and L-glutamine.
 8. The method according toclaim 5 wherein about 4 grams of said powder is reconstituted in waterto make about 30 ml and has an osmolality of 300 to 400 mOsm/kg H₂O. 9.The method according to claim 5 wherein said hypoallergenic medical foodcomprises, based on 100 grams of powder; 14.3 protein equivalent; 22.6 glipid; 46.7 g carbohydrate; 2.85 g linoleic acid; 0.48 g □-linolenicacid; 515 mg calcium; 385 mg phosphorous; 390 mcg Vitamin A; 5 mcg VitamD; 6.7 mg Vitamin E; 30 mcg Vitamin K; 1.0 mg thiamine; 0.50 mgriboflavin; 0.48 mg Vitamin B-6; 2.0 mcg Vitamin B-12; 8.0 mg niacin;140 mcg folic acid; 2.0 mg pantothenic acid; 20 mcg biotin; 43 mgVitamin C; 38 mg choline; 24 mg inositol; 23 mg L-carnitine; 40 mgmagnesium; 8.4 mg iron; 5.3 mg zinc; 0.50 mg manganese; 0.60 mg copper;34 mcg iodine; 11 mcg selenium; 11 mcg chromium; 12 mcg molybdenum; 9.35mEq sodium; 18.29 mEq potassium and 8.04 mEq chloride.
 10. The methodaccording to claim 8 wherein said reconstituted powder has a Caloricdensity of about 0.68 kcalories/ml and an osmolality of 350 to 375mOsm/kg H₂O.
 11. A method for the nutritional support of a humansuffering from a malady selected from the group consisting of severefood allergies, short gut syndrome, cystic fibrosis, pancreatic disease,gastroenteritis, inflammatory bowel disease, intractable diarrhea,malnutrition, protein maldigestion, necrotizing enterocolitis,infectious diseases, hypermetabolism, trauma, eosinophilicgastroenteritis and gastroesophogeal reflux; said method comprising theadministration to said human of a hypoallergenic medical food suitablefor use as the sole source of nutrition comprising: a) a carbohydratecomponent which comprises from 38 to 56% of the total Caloric content ofsaid food; b) a lipid component which comprises from 38 to 50% of thetotal Caloric content of said food and in which said lipid componentcomprises, based upon the weight of the lipid component, 35 to 43%high-oleic safflower oil, 28 to 35% fractionated coconut oil, 0.5 to 8%esterified glycerols and 24 to 30% soy oil; and c) a free amino acidcomponent which comprises from 10 to 20% of the total Caloric content ofsaid food and wherein said amino acid component comprises, based uponthe weight of the hypoallergenic food, less than 50 ppm of L-glutamicacid and less than 50 ppm of L-aspartic acid.
 12. The method accordingto claim 11 wherein said hypoallergenic medical food comprises, based on100 kcalories of said composition: 2.8 to 3.8 g protein equivalent; 4.0to 5.6 g fat, 9.0 to 11.8 g carbohydrate; 0.4 to 0.8 g linoleic acid;262 to 475 IU Vitamin A; 40 to 80 IU Vitamin D; 2.0 to 3.5 IU Vitamin E;5 to 20 mcg Vitamin K; 0.11 to 0.42 mg thiamine, 0.1 to 0.21 mgriboflavin; 0.09 to 0.17 mg Vitamin B-6; 0.40 to 1.36 mcg Vitamin B-12;1.6 to 3.2 mg niacin; 28 to 60 mcg folic acid; 0.40 to 1.70 mgpantothenic acid; 4.0 to 18.0 mcg biotin; 8.6 to 85 mg Vitamin C; 7.5 to14.6 mg choline; 4.6 to 9.9 mg inositol; 4.0 to 6.5 mg L-carnitine; 103to 127 mg calcium; 76 to 103 mg phosphorus; 8.0 to 12.7 mg magnesium;1.6 to 2.4 mg iron; 1.0 to 1.7 mg zinc; 0.10 to 0.15 mg manganese; 0.11to 0.19 mg copper; 6.7 to 11.8 mcg iodine; 2.2 to 4.7 mcg selenium; 2.2to 4.7 mcg chromium; 2.4 to 5.5 mcg molybdenum; 40 to 55 mg sodium; 144to 174 mg potassium and 55 to 85 mg chloride.
 13. The method accordingto claim 1 wherein said free amino acid component comprises, based uponthe weight of the free amino acid component: 2.3 to 3.2 wt%—L-histidine; 5.9 to 8.5 wt %—L-isoleucine; 9.5 to 14.0 wt %—L-leucine;6.6 to 9.7 wt %—L-valine; 5.2 to 7.6 wt %—L-lysine; 2.2 to 3.2 wt%—L-methionine; 4.9 to 7.1 wt %—L-phenylalanine; 3.8 to 5.7 wt%—L-threonine; 1.4 to 2.2 wt %—L-tryptophan; 3.0 to 4.2 wt %—L-alanine;5.3 to 7.7 wt %—L-arginine; 8.6 to 12.4 % L-asparagine monohydrate; 1.1to 1.9%—L-cystine dihydrochloride; 11.0 to 15.8 wt %—L-glutamine; 2.3 to3.2 wt %—glycine; 3.0 to 4.1 wt % L-proline; 3.0 to 4.2 wt %—L-serine;and 5.0 to 7.1 wt %—L-tyrosine.
 14. The method according to claim 1wherein said carbohydrate component consists essentially of corn syrupsolids with a DE of 23 or less.
 15. The method according to claim 1wherein said hypoallergenic medical food is in powder form.
 16. Themethod according to claim 15 wherein about 4 grams of said powder isreconstituted in water to make about 30 ml and has an osmolality of 300to 400 mOsm/kg H₂O.
 17. The method according to claim 1 wherein saidhypoallergenic medical food additionally comprises at least one elementselected from the group consisting of nucleosides, nucleotides,antioxidant system, natural flavor, artificial flavors, artificialsweeteners, major trace and ultratrace minerals, minerals, vitamins andm-inositol.
 18. The method according to claim 16 wherein saidreconstituted powder has a Caloric density of about 0.68 kcalories/mland an osmolality of 350 to 375 mOsm/kg H₂O.
 19. The method according toclaim 15 wherein said hypoallergenic medical food comprises, based on100 grams of powder: 1.43 g protein equivalent; 22.6 g lipid; 46.7 gcarbohydrate; 2.85 g linoleic acid; 0.48 g □-linolenic acid; 515 mgcalcium; 385 mg phosphorous; 390 mcg Vitamin A; 5 mcg Vitamin D; 6.7 mgVitamin E; 30 mcg Vitamin K; 1.0 mg thiamine; 0.50 mg riboflavin; 0.48mg Vitamin B-6; 2.0 mcg Vitamin B-12; 8.0 mg niacin; 140 mcg folic acid;2.0 mg pantothenic acid; 20 mcg biotin; 43 mg Vitamin C; 38 mg choline;24 mg inositol; 23 mg L-carnitine; 40 mg magnesium; 8.4 mg iron; 5.3 mgzinc; 0.50 mg manganese; 0.60 mg copper; 34 mcg iodine; 11 mcg selenium;11 mcg chromium; 12 mcg molybdenum; 9.35 mEq sodium; 18.29 mEq potassiumand 8.04 mEq chloride.
 20. The method according to claim 1 wherein saidcarbohydrate component is corn syrup solids with a DE of 23 or less;said lipid component comprises 35 to 41% by wt high oleic safflower oil,28 to 35% by wt fractionated coconut oil, 24 to 30% by wt soy oil and0.5 to 8% by wt of diacetyl tartaric acid esters of monoglycerides; andsaid free amino acid component comprises L-asparagine monohydrate andL-glutamine.